Lin Qinghong, Wang Xuejun, Peng Xiaoliao, Han Xiaosong, Zhang Xiaoyu, Sun Ling, Wang Yan, Liu Shengtao, Zhou Xingtao
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.
Eye Institute and Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, China.
Front Genet. 2025 Jun 6;16:1603019. doi: 10.3389/fgene.2025.1603019. eCollection 2025.
This study reports a three-generation Chinese family with polymorphous corneal dystrophy subtype 3 (PPCD3) and keratoconus (KC) aggravation induced by corneal refractive surgery, specifically small incision lenticule extraction (SMILE), in the context of genetic variations.
The history of illnesses and blood samples of all family members were collected. One hundred healthy individuals served as normal controls. We conducted whole exome sequencing on genomic DNA and sanger sequencing to verify the variants between all controls and family members.
Three family members were previously diagnosed with subclinical keratoconus (III1 and III2 preoperatively, and II2). Both the proband (III1) and her younger brother (III2) underwent SMILE to correct refractive errors. One year later, visual acuity of III1 decreased significantly with KC aggravation and corneal opacification. The KC of III2 progressed significantly 6 months after surgery. Both were subsequently diagnosed with PPCD3. We detected both Zinc finger E-box-binding homeobox 1 (ZEB1) gene and zinc finger protein 469 (ZNF469) gene pathogenic variant in the proband and another two patients in this family, including a heterozygous missense variation c.13C>G (p.P5A, rs753301298) in the gene, and a heterozygous non-frameshift variant c. 3093_3104del (p.D1035_K1038del) in the gene. The variants including c.13C>G in and c.3093_3104del in were speculated to be pathogenic or a variant of uncertain significance by online prediction software.
This study demonstrated the importance of a thorough ocular examination, especially the cornea, and a gene screening before SMILE.
本研究报告了一个三代中国家庭，该家庭患有3型多形性角膜营养不良（PPCD3），且在基因变异的情况下，角膜屈光手术，特别是小切口透镜切除术（SMILE）诱发了圆锥角膜（KC）加重。
收集了所有家庭成员的病史和血液样本。100名健康个体作为正常对照。我们对基因组DNA进行了全外显子组测序，并进行桑格测序以验证所有对照与家庭成员之间的变异。
三名家庭成员先前被诊断为亚临床圆锥角膜（III1和III2术前，以及II2）。先证者（III1）和她的弟弟（III2）均接受了SMILE以矫正屈光不正。一年后，III1的视力显著下降，伴有KC加重和角膜混浊。III2的KC在术后6个月显著进展。两人随后均被诊断为PPCD3。我们在该家系的先证者和另外两名患者中检测到锌指E盒结合同源框1（ZEB1）基因和锌指蛋白469（ZNF469）基因的致病变异，包括该基因中的杂合错义变异c.13C>G（p.P5A，rs753301298），以及该基因中的杂合非移码变异c.3093_3104del（p.D1035_K1038del）。在线预测软件推测，包括该基因中的c.13C>G和该基因中的c.3093_3104del在内的变异为致病或意义未明的变异。
本研究证明了在进行SMILE之前进行全面眼部检查，尤其是角膜检查和基因筛查的重要性。
